TY - JOUR
T1 - Modulatory effects of low-dose hydrogen peroxide on the function of human plasmacytoid dendritic cells
AU - Pazmandi, Kitti
AU - Magyarics, Zoltan
AU - Boldogh, Istvan
AU - Csillag, Aniko
AU - Rajnavolgyi, Eva
AU - Bacsi, Attila
N1 - Funding Information:
This work was supported by the Hungarian Scientific Research Fund (K-73347 to A.B. and NK-72937 to E.R.), the U.S. National Institute of Environmental Health Science (RO1-ES018948 to I.B.), the U.S. National Institute of Allergic and Infectious Diseases (AI062885-01 to I.B.), and the TAMOP 4.2.1/B-09/1/KONV-2010-0007 project (to A.B. and E.R.). The project is cofinanced by the European Union and the European Social Fund.
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Under normal conditions, plasmacytoid dendritic cells (pDCs) are located in peripheral lymphoid organs or circulate in the blood, from where they can migrate to sites of infection or inflammation. In inflamed tissues, pDCs can be exposed to elevated levels of reactive oxygen species produced by inflammatory cells and we presume that oxidative stress could affect the cellular responses of pDCs to microenvironmental stimuli. To explore this possibility, human pDCs isolated from peripheral blood of healthy donors were treated with H 2O 2 and R837 (a Toll-like receptor 7 ligand), separately and in combination. Our results demonstrate that treatment with a low concentration (0.01 μM) of H 2O 2 resulted in only slight changes in the expression of CD40, CD80, CD86, and CD83; however, low-dose H 2O 2 markedly decreased the expression of HLA-DQ on pDCs. Exposure to H 2O 2 did not trigger the release of IL-6, TNF-α, IL-8, or IFN-α from pDCs. Although addition of H 2O 2 did not modify the capacity of pDCs to activate allogeneic IL-17- or IFN-γ-producing T cells, it significantly increased the ability of pDCs to stimulate IL-4-secreting T cells. Exposure of pDCs to H 2O 2 before cocultivation with naïve autologous T cells significantly lowered IL-10 production by T cells, but did not affect IL-17 release. It was also observed that H 2O 2-exposed pDCs provided stronger stimuli for Th2 than for Th1 differentiation upon autologous activation, compared to untreated pDCs, possibly because of elevated surface expression of OX40-L. Most importantly, when pDCs were stimulated with R837 in the presence of H 2O 2, decreased phenotypic activation, decreased chemokine and cytokine release, and impaired allo- and autostimulatory functions of pDCs were detected, indicating that pDCs exposed to oxidative stress in vivo may have an anti-inflammatory or tolerogenic role in regulating adaptive immune responses.
AB - Under normal conditions, plasmacytoid dendritic cells (pDCs) are located in peripheral lymphoid organs or circulate in the blood, from where they can migrate to sites of infection or inflammation. In inflamed tissues, pDCs can be exposed to elevated levels of reactive oxygen species produced by inflammatory cells and we presume that oxidative stress could affect the cellular responses of pDCs to microenvironmental stimuli. To explore this possibility, human pDCs isolated from peripheral blood of healthy donors were treated with H 2O 2 and R837 (a Toll-like receptor 7 ligand), separately and in combination. Our results demonstrate that treatment with a low concentration (0.01 μM) of H 2O 2 resulted in only slight changes in the expression of CD40, CD80, CD86, and CD83; however, low-dose H 2O 2 markedly decreased the expression of HLA-DQ on pDCs. Exposure to H 2O 2 did not trigger the release of IL-6, TNF-α, IL-8, or IFN-α from pDCs. Although addition of H 2O 2 did not modify the capacity of pDCs to activate allogeneic IL-17- or IFN-γ-producing T cells, it significantly increased the ability of pDCs to stimulate IL-4-secreting T cells. Exposure of pDCs to H 2O 2 before cocultivation with naïve autologous T cells significantly lowered IL-10 production by T cells, but did not affect IL-17 release. It was also observed that H 2O 2-exposed pDCs provided stronger stimuli for Th2 than for Th1 differentiation upon autologous activation, compared to untreated pDCs, possibly because of elevated surface expression of OX40-L. Most importantly, when pDCs were stimulated with R837 in the presence of H 2O 2, decreased phenotypic activation, decreased chemokine and cytokine release, and impaired allo- and autostimulatory functions of pDCs were detected, indicating that pDCs exposed to oxidative stress in vivo may have an anti-inflammatory or tolerogenic role in regulating adaptive immune responses.
KW - Free radicals
KW - Immune regulation
KW - Inflammation
KW - Oxidative stress
KW - Plasmacytoid dendritic cells
UR - http://www.scopus.com/inward/record.url?scp=84856285630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856285630&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2011.11.022
DO - 10.1016/j.freeradbiomed.2011.11.022
M3 - Article
C2 - 22178414
AN - SCOPUS:84856285630
SN - 0891-5849
VL - 52
SP - 635
EP - 645
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 3
ER -